Is PIEZO1 p.Phe44= (c.132C>T) pathogenic?

PIEZO1 p.Phe44= (c.132C>T) is classified Benign/Likely benign in PIEZO1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-07). Low-frequency (popmax 4.08%, afr); Associated with dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema.

How common is PIEZO1 p.Phe44= (c.132C>T) in the general population?

PIEZO1 p.Phe44= (c.132C>T) is low-frequency (popmax 4.08%, afr) (gnomAD).

How is Dehydrated hereditary stomatocytosis inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

PIEZO1 p.Phe44=

Q: What condition is associated with PIEZO1 p.Phe44= (c.132C>T)?

PIEZO1 p.Phe44= (c.132C>T) is associated with dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema, lymphatic malformation 6 (ClinVar).

c.132C>T · rs112488313 · VCV709313

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.08%, afr)

Conditions

dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.16	GERP -4, phastCons 0.11
Overall
CADD	2.081	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.08% African / African-American · 2,935/71,936 alleles

Filtering AF 3.96% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.91%

Overall 0.276% 4,193/1,520,894 alleles · low-frequency exomes 2,357/1,368,556 · genomes 1,836/152,338 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.08%	25
Ashkenazi Jewishnot grpmax-eligible	1.46%	68
Remaining individualsnot grpmax-eligible	0.466%	214
Admixed American	0.351%	285
Middle Eastern	0.324%	309
European (non-Finnish)	0.0323%	3,100
South Asian	0.00988%	10,121

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PIEZO1
Protein: p.Phe44=
Coding: c.132C>T
MANE Select: NM_001142864
dbSNP: rs112488313
Type: single nucleotide variant
Location: chr16:88749412 (GRCh38)
Gene constraint: LOEUF 1.17 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.74 · 6 PDB

Full PIEZO1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dehydrated hereditary stomatocytosis with or without pseudohyperkalemia and/or perinatal edema — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: lymphatic malformation 6

For Dehydrated hereditary stomatocytosis (Orphanet):

Inheritance: Autosomal dominant
Onset: Antenatal, Neonatal
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

PIEZO1 p.Phe44Ile Uncertain significance ★ ⚠ same residue
PIEZO1 p.Ala2003Asp Likely pathogenic ★★ same condition
PIEZO1 p.Ala2020Thr Pathogenic/Likely pathogenic ★★ same condition
PIEZO1 p.Arg1164Ter Pathogenic/Likely pathogenic ★★ same condition
PIEZO1 p.Arg2456His Pathogenic ★★ same condition
PIEZO1 p.Gln1125Ter Pathogenic/Likely pathogenic ★★ same condition
PIEZO1 p.Gln422Ter Pathogenic ★★ same condition
PIEZO1 p.Glu1764Ter Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/piezo1-p-phe44 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown